FATTY ACID ETHYL ESTERS: BIOLOGICAL MARKERS OF ALCOHOL

与零级代谢物不同，乙醛、乙酸乙酯 酯(FAEE)是一阶直接的、非氧化性的代谢物 我们实验室于1981年描述的乙醇将由 FAEE合成酶。我们广泛的方法 这些脂类的提取和定量研究进展 生物样本导致观察到FAEE是 在体内脂肪组织和骨髓中形成，有一半- 寿命约为24小时，比乙醇的寿命长得多。 在初步实验中，浓度高达5400nmol/g 在兔脂肪组织和骨髓中发生，限制为 可检测性为2nmol/g；类似地，尸检研究揭示 脂肪组织中这些酒精代谢物的存在 酒鬼。在一项初步的临床研究中，骨髓的定量 FAEE允许正确诊断饮酒 在摄入五分之四的酒精后长达六天的时间 消费者，以及八分之八的控制程序。无误报 因此被检测到。重要的是，FAEE合成酶活性具有 在人外周血白细胞中被定量。建议 因此，研究将表征比率的有用性。 脂肪组织和骨髓FAEE对白细胞的浓度 FAEE合酶活性作为酒精生物标志物的研究 与合成酶基因多态无关的消耗 活动。第一，脂肪的时间进程和浓度 组织和骨髓FAEE将在喂养的兔身上进行定量 不同数量的乙醇最多三个月和价值 归一化为白细胞FAEE合成酶活性。脂肪组织 将对FAEE合成酶进行表征。人类研究将包括 800例患者脂肪组织FAEE定量分析 常规普外科手术和与所获得的结果相关的结果 通过标准问卷评估频率、持续时间和 最近饮酒的数量。阿司匹林的药代动力学分析 经皮针抽吸获得臀部脂肪组织 将对40名患者进行骨髓FAEE检查 在临床研究中心使用乙醇 外周血白细胞FAEE浓度的归一化 FAEE合酶活性。这些数据将确定 组织FAEE/白细胞合酶指数的定量有用性 作为诊断医疗中使用的酒精消费的标志 评估、法医案例、高风险工作人员和监督 有问题的饮酒者拒绝饮酒。

Unlike the zero order metabolite, acetaldehyde, fatty acid ethyl esters (FAEE) are first order direct, nonoxidative metabolites of ethanol described in our laboratory in 1981 to be formed by the enzyme FAEE synthase. Our extensive methodological development for extraction and quantitation of these lipids from biological samples has led to the observation that FAEE are formed in vivo in adipose tissue and bone marrow and have a half- life of approximately 24 hours, much longer than that of ethanol. In preliminary experiments, concentrations as high as 5400 nmol/g occur in rabbit adipose tissue and bone marrow with a limit of detectability of 2 nmol/g; similarly, autopsy studies disclose the presence of these alcohol metabolites in adipose tissues of drinkers. In a pilot clinical study, quantitation of bone marrow FAEE allowed the correct diagnosis of alcohol consumption to be made as long as six days after ingestion in four out of five alcohol consumers, and in eight out of eight controls. No false positives were thus detected. Importantly, FAEE synthase activity has been quantitated in peripheral human leukocytes. Proposed studies therefore will characterize the usefulness of the ratio of adipose tissue and bone marrow FAEE concentration to leukocyte FAEE synthase activity as biological markers of alcohol consumption that is independent of polymorphisms in synthase activity. First, the time course and concentration of adipose tissue and bone marrow FAEE will be quantitated in rabbits fed various amounts of ethanol for up to three months and values normalized to leukocyte FAEE synthase activity. Adipose tissue FAEE synthase will be characterized. Human studies will consist of adipose tissue FAEE quantitation in 800 patients undergoing routine general surgery and results correlated to those obtained by a standard questionnaire to assess frequency, duration and quantity of recent alcohol use. Pharmacokinetic analyses of buttock adipose tissue obtained by skinny needle aspiration and bone marrow FAEE will be performed in forty patients administered ethanol in the Clinical Research Center with normalization of FAEE concentrations to peripheral leukocyte FAEE synthase activity. These data will establish the quantitative usefulness of a tissue FAEE/leukocyte synthase index as a marker of alcohol consumption for use in diagnostic medical evaluations, forensic cases, high risk job holders, and surveillance in problem drinkers who deny alcohol ingestion.